Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium.
Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium.
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DOI：
10.1158/1055-9965.epi-15-0874
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Troester MA
中科院分区：
文献类型：
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作者：
Allott EH;Cohen SM;Geradts J;Sun X;Khoury T;Bshara W;Zirpoli GR;Miller CR;Hwang H;Thorne LB;O'Connor S;Tse CK;Bell MB;Hu Z;Li Y;Kirk EL;Bethea TN;Perou CM;Palmer JR;Ambrosone CB;Olshan AF;Troester MA
将乳腺癌分类为内在亚型具有临床和流行病学重要性。为了检查基于免疫组织化学 (IHC) 的方法识别内在亚型的准确性，将三生物标志物 IHC 组与临床记录和基于 RNA 的内在 (PAM50) 亚型进行了比较。对来自非裔美国人乳腺癌流行病学和风险 (AMBER) 联盟的 1,920 例病例进行 IHC 染色的组织微阵列 (TMA) 进行雌激素受体 (ER)、孕激素受体 (PR) 和 HER2 的自动评分。多个核心（1-6/病例）被折叠以对病例进行分类，并将自动评分与临床记录和基于 RNA 的亚型进行比较。三种生物标志物 IHC 组的自动分析与临床记录高度一致（ER 和 HER2 为 93%，PR 为 88%）。肿瘤细胞含量低和核心尺寸较小的病例与临床记录的一致性降低。无论激素受体阳性阈值如何（1% 与 10%），基于 IHC 的定义都与临床记录高度一致，但 10% 阈值与基于 RNA 的内在亚型的一致性最高。使用 10% 阈值，基于 IHC 的定义识别出具有高敏感性 (86%) 的 basal-like 内在亚型，而 Luminal A、Luminal B 和 HER2 富集亚型的敏感性较低（分别为 76%、40% 和 37%）。基于 IHC 的三种生物标志物亚型对于区分基底样和非基底样具有合理的准确性，而需要额外的生物标志物才能准确分类 Luminal A、Luminal B 和 HER2 富集的癌症。依赖三种生物标志物 IHC 状态进行亚型分类的流行病学研究在区分 Luminal A 和 Luminal B 以及解释富含 HER2 的癌症的结果时应谨慎行事。
Classification of breast cancer into intrinsic subtypes has clinical and epidemiologic importance. To examine accuracy of immunohistochemistry (IHC)-based methods for identifying intrinsic subtypes, a three-biomarker IHC panel was compared to the clinical record and RNA-based intrinsic (PAM50) subtypes. Automated scoring of estrogen receptor (ER), progesterone receptor (PR) and HER2 was performed on IHC-stained tissue microarrays (TMAs) comprising 1,920 cases from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Multiple cores (1–6/case) were collapsed to classify cases, and automated scoring was compared to the clinical record and to RNA-based subtyping. Automated analysis of the three-biomarker IHC panel produced high agreement with the clinical record (93% for ER and HER2, and 88% for PR). Cases with low tumor cellularity and smaller core size had reduced agreement with the clinical record. IHC-based definitions had high agreement with the clinical record regardless of hormone receptor positivity threshold (1% vs. 10%), but a 10% threshold produced highest agreement with RNA-based intrinsic subtypes. Using a 10% threshold, IHC-based definitions identified the basal-like intrinsic subtype with high sensitivity (86%), while sensitivity was lower for luminal A, luminal B and HER2-enriched subtypes (76%, 40% and 37%, respectively). Three-biomarker IHC-based subtyping has reasonable accuracy for distinguishing basal-like from non-basal-like, while additional biomarkers are required for accurate classification of luminal A, luminal B and HER2-enriched cancers. Epidemiologic studies relying on three-biomarker IHC status for subtype classification should use caution when distinguishing luminal A from luminal B and when interpreting findings for HER2-enriched cancers.